2-Methyl-5-(tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidine → (S)-6-(3-(Hydroxymethyl)pyrrolidin-1-yl)-5-(2-methylpyrimidin-5-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide

HRID 923902Notes

Reaction equation

HRID 923902 reaction equation
Br[C:2]1[C:3]([N:22]2[CH2:26][CH2:25][C@H:24]([CH2:27][OH:28])[CH2:23]2)=[N:4][CH:5]=[C:6]([CH:21]=1)[C:7]([NH:9][C:10]1[CH:15]=[CH:14][C:13]([O:16][C:17]([F:20])([F:19])[F:18])=[CH:12][CH:11]=1)=[O:8].[CH3:29][C:30]1[N:35]=[CH:34][C:33](B2OC(C)(C)C(C)(C)O2)=[CH:32][N:31]=1>>[OH:28][CH2:27][C@H:24]1[CH2:25][CH2:26][N:22]([C:3]2[C:2]([C:33]3[CH:32]=[N:31][C:30]([CH3:29])=[N:35][CH:34]=3)=[CH:21][C:6]([C:7]([NH:9][C:10]3[CH:15]=[CH:14][C:13]([O:16][C:17]([F:20])([F:19])[F:18])=[CH:12][CH:11]=3)=[O:8])=[CH:5][N:4]=2)[CH2:23]1

Participants

3

Reactant 2

HCID 457872822-Methyl-5-(tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidineHCID 86702601(S)-5-bromo-6-(3-(hydroxymethyl)pyrrolidin-1-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide

Product 1

HCID 89908446(S)-6-(3-(Hydroxymethyl)pyrrolidin-1-yl)-5-(2-methylpyrimidin-5-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide

Procedure

The title compound was prepared in an analogous fashion to that described in Example 75 using (S)-5-bromo-6-(3-(hydroxymethyl)pyrrolidin-1-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 78.1) and 2-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidine to afford an off-white solid. UPLC-MS (condition 1) tR=2.37 min, m/z=474.1 [M+H]+, m/z=472.1 [M−H]−; 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.51-1.65 (m, 1H) 1.79-1.90 (m, 1H) 2.17-2.30 (m, 1H) 2.68 (s, 3H) 2.99 (dd, J=10.76, 6.85 Hz, 1H) 3.11-3.23 (m, 2H) 3.22-3.30 (m, 3H) 4.61 (br. s, 1H) 7.35 (d, J=8.80 Hz, 2H) 7.85 (d, J=9.05 Hz, 2H) 8.04 (d, J=2.45 Hz, 1H) 8.76 (s, 2H) 8.77 (d, J=2.44 Hz, 1H) 10.15 (s, 1H).

Workup

  1. customto afford an off-white solid

Sources & evidence

ORD record
ord-4b36b8faf1aa42f58c01dbef63fcabba
Source dataset
uspto-grants-2016_03
Patent number
US09278981B2

Reaction notes

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